Liposome treatment of viral infections

Abstract

One can treat a viral infection such as hepatitis B (HBV), hepatitis C(HCV), and bovine viral diarrhea virus (BVDV) infections via the delivery of pH sensitive liposomes directly into the endoplasmic reticulum (ER) membrane. Two exemplary liposome formulations are DOPE/CHEMS (DC liposomes) and DOPE/CHEMS/PEG-PE (DCPP liposomes). DC and DCPP liposomes can optimize the intracellular delivery of N-butyl deoxynojirimycin (NB-DNJ), and consequently increase the in vivo activity of this iminosugar several orders of magnitude, and could be used in combination with other therapeutic agents such as interferon and/or ribavirin. The optimized release of NB-DNJ directly into the ER can be also applied for the treatment of other viruses, for which NB-DNJ is known to be an effective antiviral, such as human immunodeficiency virus (HIV).

1 . A method of treating a viral infection, comprising
 administering to a host in need thereof a composition comprising   (a) a liposome comprising DOPE and CHEMS lipids and   (b) one or more compounds encapsulated into the liposome,   
       wherein the viral infection is an ER membrane budding viral infection or a plasma membrane budding viral infection; 
       wherein the one or more compounds comprise N-butyl deoxynojirimycin (NB-DNJ) and 
       wherein said administering results in delivering of the one or more compounds into an endoplasmic reticulum of a cell, that is infected with a virus causing the infection, and incorporating one or more lipids of the liposome in an endoplasmic reticulum membrane of the cell. 
     
     
         2 . The method of  claim 1 , wherein the infection is an ER membrane budding viral infection. 
     
     
         3 . The method of  claim 2 , wherein the infection is an HCV infection. 
     
     
         4 . The method of  claim 2 , wherein the infection is a BVDV infection. 
     
     
         5 . The method of  claim 2 , wherein the one or more compounds further comprise a nucleoside/nucleotide antiviral agent, an immunostimulating/immunomodulating agent or a combination thereof. 
     
     
         6 . The method of  claim 5 , wherein the nucleoside/nucleotide antiviral agent is ribavirin and the immunostimulating/immunomodulating agent is interferon alpha. 
     
     
         7 . The method of  claim 1 , wherein the infection is a plasma membrane budding viral infection. 
     
     
         8 . The method of  claim 7 , wherein the infection is an HIV infection. 
     
     
         9 . The method of  claim 8 , wherein the one or more compounds further comprise at least one anti-HIV compound. 
     
     
         10 . The method of  claim 1 , wherein the liposome is a DC liposome. 
     
     
         11 . The method of  claim 1 , wherein the liposome further comprises PEG-PE lipids. 
     
     
         12 . The method of  claim 11 , wherein the liposome is a DCPP liposome. 
     
     
         13 . The method of  claim 1 , wherein the liposome further comprises PI lipids. 
     
     
         14 . The method of  claim 13 , wherein a molar concentration of the PI lipids in the liposome is from 5 to 50%. 
     
     
         15 . The method of  claim 14 , wherein the molar concentration of the PI lipids in the liposome is from 10 to 30%. 
     
     
         16 . The method of  claim 1 , wherein the host is a human. 
     
     
         17 . A method of treating a viral infection, comprising administering to a host in need thereof a composition comprising
 (a) a liposome comprising DOPE, CHEMS and PEG-PE lipids and   (b) one or more compounds encapsulated into the liposome,   
       wherein the one or more compounds comprise N-butyl deoxynojirimycin (NB-DNJ). 
     
     
         18 . The method of  claim 17 , wherein the virus is hepatitis C virus. 
     
     
         19 . The method of  claim 17 , wherein the virus is BVDV virus. 
     
     
         20 . The method of  claim 19 , wherein the virus is a ncp strain of the BVDV virus. 
     
     
         21 . The method of  claim 19 , wherein the virus is a cp strain of the BVDV virus 
     
     
         22 . The method of  claim 17 , wherein the one or more compounds further comprise a nucleoside/nucleotide antiviral agent, an immunostimulating/immunomodulating agent or a combination thereof. 
     
     
         23 . The method of  claim 22 , wherein the nucleoside/nucleotide antiviral agent is ribavirin and the immunostimulating/immunomodulating agent is interferon. 
     
     
         24 . The method of  claim 17 , wherein the virus is an HIV virus. 
     
     
         25 . The method of  claim 24 , wherein the HIV virus is selected from a group consisting of 92UG037, 92RW021, JR-FL, 92HT599, 89.6, 93IN101, 97USNG30, 92UG021, 92UG046 and 93BR020 primary HIV-1 isolates. 
     
     
         26 . The method of  claim 24 , wherein the one or more compounds further comprise one or more anti-HIV agents. 
     
     
         27 . The method of  claim 17 , wherein the host is a human. 
     
     
         28 . The method of  claim 17 , wherein the liposome further comprises PI lipids. 
     
     
         29 . The method of  claim 28 , wherein a molar concentration of the PI lipids in the liposome is from 5 to 50%. 
     
     
         30 . The method of  claim 29 , wherein the molar concentration of the PI lipids in the liposome is from 10 to 30%.